Cord blood cytokines/chemokines linked to delays in toddlers exposed to SARS-CoV-2 prenatally

Background: Maternal infections are linked to neurodevelopmental impairments, highlighting the need to investigate SARS-CoV-2-induced immune activation. Objective: This study aimed to evaluate the impact of maternal infection on neurodevelopment and investigate whether cytokine and chemokine profiles predict delays at 24 months. Methods: Conducted in Brazil (January 2021–March 2022), this follow-up study included 18 SARS-CoV-2 positive pregnant women at 35–37 weeks’ gestation, 15 umbilical cord blood samples, and blood samples from 15 children at 6 months and 14 at 24 months. Developmental delay was defined using the Bayley Scales of Infant and Toddler Development, Third Edition, with scores below 90 in cognitive, communication, or motor domains. Results: At 6 months, 33.3% of infants exhibited cognitive delays, 20% communication delays, and 40% motor delays, increasing to 35.71%, 64.29%, and 57.14% at 24 months, respectively. Elevated interferon-gamma and tumor necrosis factor-alpha in cord blood correlated with cognitive delays, while interleukin (IL)-6, IL-8, IL-17, and IL-1β were associated with motor delays. Increased C-X-C motif chemokine ligand 10 and other cytokines were associated with communication delays. Conclusion: Maternal SARS-CoV-2 may impact infant neurodevelopment, as early cytokine elevations correlate with delays, highlighting the importance of early monitoring and interventions to reduce long-term effects. Impact: Prenatal SARS-COV-2 infection in pregnant women is linked to developmental delays in toddlers, with cytokine and chemokine changes associated with neurodevelopmental outcomes at 24 months. This study shows the long-term impact of maternal SARS-COV-2 infection on child development, highlighting inflammatory markers like IFN-γ, TNFα, IL-6, IL-8, IL-17, IL-1β, and CXCL10. Identifying specific cytokines correlating with cognitive, communication, and motor delays suggests potential biomarkers for early intervention. Conducted in Fortaleza, Brazil, the study emphasizes understanding local epidemiological impacts on child development, especially in regions with high infection rates. (Figure presented.)